JPH0347250B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Technical Field The present invention relates to novel synergistic antiparasitic compositions containing active substance combinations as active ingredients and for the prevention of parasites in livestock and productive animals.
It particularly relates to the use of said composition for combating liver worms and nematodes. The active substance combination that forms the basis of the composition according to the invention has an unexpected synergistic effect that exceeds in a very advantageous manner the additive effect of the individual active substances forming the combination. The active substance combination according to the invention comprises the following individual active substances: Formula: (wherein n is 0 or 1) At least one compound and formula represented by: A compound of the formula, including isomers of the compound of the formula as well as acid addition salts of the compound of the formula. The compounds mentioned above as active substance components of the compositions according to the invention are individually known as compounds with anthelmintic action. Compounds of the formula are disclosed in DE 2815621, and compounds of the formula are disclosed in U.S. Pat. , Tetrahedron
Letters 1967 , 1467 and Am.Journ.Vet.Res.
32, 545 (1971). For combating parasites, the combination of different chemicals to obtain a synergistic enhancement of activity is of increasing importance. This is because the combination can effectively prevent the more frequent resistance of parasites to the individual compounds. The necessary increased amounts of active substance used to overcome this increased resistance of the parasite can therefore be largely avoided. The savings in the amount of active substance applied has significant economic and ecological advantages by reducing environmental pollution. In the administration of anthelmintics to productive animals, it refers to successive doses or dose reductions that may lead to resistance, which at the same time relates to a reduction in the level of toxicity in the treated animals, thus reducing their effectiveness during treatment. production. Parasitic diseases in livestock and productive animals are well known and widespread, and these diseases result in reduced growth and productivity, and often death, of the affected animals. A particularly dangerous parasitic disease is Fasciolose, which is a disease of the liver fluke parasites (e.g. Fasciola and Fasciola
gigantica)), and this occurs particularly in ruminants, such as sheep and calves. Losses due to this parasitic disease are considered to be substantial, especially when the disease is endemic in a herd of calves. Therefore, the eradication and prevention of phaasciolosis is considered an urgent problem in order to avoid such losses in animal production, especially economic ruin.
Despite the fact that many preparations are known in the field of combating helminths, it has not been possible to date to develop active substances that, in addition to a good general anthelmintic action, At the same time, it is a substance that exhibits a satisfactory action against adult and larval Dystoma spp. in sheep and calves, while having low toxicity. The following facts have now been discovered. That is, the active substance combination contained in the composition according to the invention, which comprises a compound of the formula and a compound of the formula, exhibits a highly active pesticidal action and is effective against nematodes and trematodes. Not only does it have a wide range of activity against citrus, but it also has a very strong and significant effect on citrus in the sheep's body. Particularly advantageous points should be emphasized in the following facts. That is,
The combination of active substances on which the composition according to the invention is based has a comprehensive effect on liver flukes in the sheep's body in very small quantities, resulting in effective production and growth by the treated animals during treatment. Side effects that can cause damage to the body can be avoided by using small doses. The activity of the active substance combination according to the invention against citrus is significantly higher than the additive effect of the individual compounds forming the combination. Thus, animals suffering from parasitic diseases can be treated simultaneously against both nematodes and trematodes at all stages of growth by a single administration of the active substance combination according to the invention. Also specifically included are those nematodes that exhibit resistance to thiabendazole (2-[4-thiazolyl]-benzimidazole) and, in some cases, to other benzimidazole derivatives. A combination of A) and B): A 5-chloro-6-(2',3'-dichlorophenoxy)-2-methylthiobenzimidazole and B L-(-)-2,3,5, 6-tetrahydro-
6-Phenylimidazo[2.1-b]thiazole ("Levamisol") is believed to be preferred. For the active substance combinations according to the invention, the applicable weight ratios of compounds of formula to compounds of formula lie in the range from 1:5 to 5:1. 1:5～
A 1:1 combination ratio is particularly preferred to achieve synergism. The usable amount of the compound of formula is preferably less than 6 mg of active substance (AS) per kg of body weight. The anthelmintic action of the inventive active substance combination of a compound of the formula and a compound of the formula is demonstrated by the following tests. Tests on sheep infected with Hepatica hepatica and nematodes Sheep were artificially infected with Hepatica hepatica using encysted larvae. For this purpose, a 0.4% aqueous suspension of carboxymethylcellulose of encysted larvae is injected directly into the stomach of the test animal. 10,000 and 5,000 benzimidazole-resistant Trichostrongylus colubriformis and nematode infective larva L3, respectively.
Sheep are simultaneously orally infected using the same animal. Animals are divided into groups of approximately equal size for treatment and one control group. the proportion of active substance in the formula is 2-5 mg/Kg;
A combination of active substances, in which the proportion of active substance in the formula is 3-7 mg/Kg, was then applied to the test animals. During the trial, the sheep are kept in normal conditions in a shed on a small pasture. To test the effect of individual active substance combinations, the number of helminth eggs excreted with the faeces is counted using standard techniques at regular intervals after infection and administration. Continue to sacrifice the test animals;
Determine the number of surviving adult roundworms. The results obtained from the medicated and control groups are compared for evaluation purposes. Results The active substance combination on which the compositions according to the invention are based has an efficacy rate of 95-100% against Kantai.
The activity of these combinations at comparable or lower doses is therefore significantly higher than the additive effect of the individual compounds making up the combination. After administering a therapeutically effective amount of the combination of active substances, clinical trials show no signs of toxicity in the test animals, and these animals appear to be healthy as well. Example: Comparative test results Application: Kantetsu Number of animals (sheep): 19 [Table] [Table] Used to exterminate sexual helminths. The combination can be administered to the animal either in a single dose or in repeated doses, a single dose depending on the species of animal, preferably between 0.5 and 7.5 kg body weight.
mg. In some cases good effects can be obtained even with long-term administration, or alternatively smaller full doses may be sufficient. The active substances or mixtures containing them can be added to the feed or introduced into the beverage. The prepared feed preferably contains the active substance combination in a concentration of 0.005 to 0.1% by weight. The compositions can be administered orally in the form of solutions, emulsions, suspensions, powders, tablets, bolus or capsules. These formulations can be prepared, for example, using the usual solid carriers such as kaolin, talc,
It is prepared using bentonite, sodium chloride, calcium phosphate or cottonseed pomace, or alternatively using liquids that do not react with the active substance, such as oils and other solvents and diluents that are not harmful to animals. If the physical and toxicological properties of the solvent or emulsion permit, the active substance combination can also be administered to animals, for example subcutaneously, or alternatively by a pour-on-method. You can also do it. Furthermore, it is also possible to administer the active substances to animals by licking stones (salts) or molasses blocks. If the anti-parasitic composition is in the form of a feed concentrate, the main carrier used is a feed substance, such as hay, produce feed, fungi or protein concentrates. In addition to active substances, the feed also contains additives,
Vitamins, antibiotics, chemotherapeutics or other insecticides, the main antibacterial, fungicidal, anticoccidiostatic and hormonal preparations, anabolic or growth promoting substances, the quality of the meat of slaughtered cattle. Contains substances that affect or are otherwise useful to other tissues. They can also be combined with insecticides and acaricides, thereby extending the action of the composition and adapting it to the given environment. The antiparasitic composition according to the invention comprises a compound of formula and an active substance combination comprising a compound of formula, together with a suitable carrier, optionally in a dispersant or a solvent which is completely inert to the active substance. It is produced by a method known per se by mixing and grinding. The antiparasitic compositions according to the invention can be used, for example, in the following formulations: Solid formulations Granules (coated granules, impregnated granules and homogeneous granules): Water-dispersible concentrates of the active substance (wettable powders) ). Liquid preparations Solvents, pastes, emulsions, especially ready-to-use suspensions (drinks). The particle size of the carrier is approx.
Up to 0.1 mm and for granules up to 0.01-0.5 mm are advantageous. The concentration of active substance combination in solid preparations is 0.5-80%
and 0.5-50% in liquid formulations. Additives which stabilize the active substance combination and/or non-ionic, anionic and cationic active substances can also be added to these mixtures, which, for example, have good wetting agents (wetting agents) and dispersibility. (dispersant). Example Water Dispersible Powder Mixture 7.5 parts by weight of an absorbent carrier such as silicic acid, 59.4 parts by weight of a carrier such as china clay or kaolin, 0.5 parts by weight of oleic acid, 5.3 parts by weight of octylphenyl polyglycol ether, and stearyl- 25 parts by weight of an active substance combination of a compound of the formula and a compound of the formula are mixed thoroughly in a mixer along with 2.3 parts by weight of the benzimidazole derivative. The mixtures are combined and ground in a disc mill or air jet mill to a particle size of 5 to 15 μm. The hydrating agent thus obtained provides good suspension in water.

Claims (1)

[Claims] 1. As an active ingredient, the formula: (wherein n is 0 or 1) At least one compound and formula represented by: Combinations of active substances comprising a compound of the formula, including isomers of the compound and acid addition salts of the compound of the formula, in the presence of suitable carriers and/or dispersants and diluents. A synergistic composition for combating parasitic helminths, comprising: 2 As an active ingredient, 5-chloro-6-(2',
3'-dichlorophenoxy)-2-methylthiobenzimidazole and L-(-)-2,3,5,6
Composition according to claim 1, comprising an active substance combination comprising -phenylimidazo[2,1-b]-thiazole, suitable carriers and/or dispersants and diluents. 3. A composition according to claim 1 or 2, wherein the weight ratio of the compound of the formula to the compound of the formula in the active substance combination is from 1:5 to 5:1. 4. A composition according to claim 1 or 2, wherein the weight ratio of the compound of the formula to the compound of the formula in the active substance combination is from 1:5 to 1:1. 5. The composition according to any one of claims 1 to 4, wherein the composition is for controlling flukes. 6. The composition according to any one of claims 1 to 4, wherein the composition exterminates liver fluke (Fassiola hepteica). 7. Composition according to claim 1, wherein the proportion of the compound of the formula in the active substance combination is less than 6 mg of active substance (AS) per kg of body weight.